Avalglucosidase Alfa Shows Success in Late-Onset Pompe Disease

Priya S. Kishnani, MD

Data presented at the WORLDSymposium 2021 annual conference from the phase 3 COMET trial (NCT02782741) suggest that avalglucosidase alfa (Sanofi) is associated with clinically meaningful improvements in patients with late-onset Pompe disease compared with alglucosidase alfa (Lumizyme; Sanofi).¹

Treatment with the investigational enzyme replacement therapy met the primary end point of noninferiority in respiratory function, as measured by forced vital capacity percent predicted (FVC%P), with a substantial improvement from baseline out to week 49 of 2.43% (95% CI, –0.13 to 4.99; P = .0074). When assessed via superiority analysis, the P value was.0626.

Additionally, treated patients also reported significant improvements in the 6-minute walk test (6MWT), a key secondary end point, with a 30.01-meter (95% CI, 1.33-58.69) improvement from baseline. Compared to the alglucosidase alfa group, this was a 4.71% (95% CI, 0.25-9.17) greater increase in distance percent predicted.

The data were compiled and presented by Priya S. Kishnani, MD, C.L. and Su Chen Professor of Pediatrics; medical director, YT and Alice Chen Pediatrics Genetics and Genomics Center; and division chief, Medical Genetics, Duke University Medical Center, and colleagues.

“Our pipeline of investigational therapies across a range of rare diseases is unmatched within the industry and continues to grow as a result of our persistent, decades-long scientific pursuit of potential therapeutic solutions for patients in need,” said Karin Knobe, Head, Development of Rare Diseases and Rare Blood Disorders, Sanofi, in a statement.² “As trailblazers in rare diseases, we persevere to discover therapies where no other treatment options exist. We uncover potential new options for difficult-to-treat diseases and our research in Pompe disease exemplifies this, as avalglucosidase alfa is designed to improve the delivery of a deficient enzyme into the muscle cells of patients.”

WATCH NOW: The Role of Child Neurologists in Diagnosing Cerebral Palsy: Bhooma Aravamuthan, MD, DPhil

In November 2020, the FDA accepted a biologics license application (BLA) for avalglucosidase alfa for long-term enzyme replacement therapy in the treatment of patients with Pompe disease. A prescription drug user fee act (PDUFA) date has been set for May 18, 2021.³

The COMET trial included 100 patients, randomized to either avalglucosidase alfa (n = 51) or alglucosidase alfa (n = 49). In the alglucosidase alfa group, 5 discontinued treatment before the end of the primary analysis period. All of the remaining 95 patients entered the extended treatment period.

The overall change from baseline at week 49 in FVC%P for the avalglucosidase alfa treated group was 2.89% (standard deviation [±], 0.88; 95% CI, 1.13-4.65), and for the alglucosidase alfa treated group was 0.46% (±0.93; 95% CI, –1.39 to 2.31). For the 6MWT, the avalglucosidase alfa and alglucosidase alfa groups showed respective changes from baseline of 32.21 meters (±9.93; 95% CI, 12.47-51.94) and 2.19 meters (±10.40; 95% CI: -18.48 to 22.86).

Kishnani and colleagues also noted that there were “consistent positive numerical trends across muscle measures, functional endurance, and health-related Quality of Life were observed with avalglucosidase alfa compared to alglucosidase alfa” and that the agent had a more favorable safety profile to the comparative treatment. The safety findings were “consistent with previous long-term experience in the NEO1 and NEO-EXT studies, with no new safety signals.”

In total, 1 patient died in the alglucosidase alfa group of acute myocardial infarction that was deemed unrelated to treatment. The most common treatment-emergent adverse events (AEs) in the avalglucosidase alfa group were: nasopharyngitis and back pain, each in 12 (23.5%) patients, and headache in 11 (21.6%) patients. In the alglucosidase alfa group, the most common AEs were: headache in 16 (32.7%) patients; nasopharyngitis in 12 (24.5%) patients; fall in 10 (20.4%) patients; and diarrhea and myalgia, each in 8 (16.3%) patients.

REFERENCES
1. Krishnani P, Attarian S, Borges JL, et al. Efficacy and Safety Results of the Avalglucosidase alfa Phase 3 COMET Trial. Presented at: WorldSymposium. February 12, 2021. Poster 121.
2. Data presented at WORLDSymposiumTM reinforces robust rare disease pipeline and highlights additional clinical data for investigational avalglucosidase alfa in Pompe disease. News release. February 2, 2021. Accessed February 12, 2021. sanofi.com/en/media-room/press-releases/2021/2021-02-02-14-00-00
3. FDA grants priority review for avalglucosidase alfa, a potential new therapy for Pompe disease. News release. Sanofi. November 18, 2020. Accessed February 12, 2021. news.sanofi.us/2020-11-18-FDA-grants-priority-review-for-avalglucosidase-alfa-a-potential-new-therapy-for-Pompe-disease